The physicochemical and kinetic properties of purified rabbit and beef skeletal muscle cyclic AMP-dependent protein kinase will be investigated. The enzyme will be crystallized and X-ray crystallographic studies will be carried out in collaboration with a different laboratory. Primary structural studies will be carried out on the holoenzyme and its subunits. Kinetic studies will be directed toward the elucidation of the mechanism of the protein kinase reaction. Comparative studies will be carried out with protein kinases derived from tissues other than skeletal muscle. The regulation of protein kinase activity by metabolites other than cyclic AMP will be studied. Specificity measurements will be made with the end in view of elucidating the relative importance of the primary, secondary and tertiary structure of protein substrates in protein phosphorylation reactions. The subunit structure of muscle and liver phosphorylase kinase, together with other physicochemical parameters, will be investigated. The mechanism of action of Ca2 plus as an activator of the muscle enzyme will be explored. Phosphoprotein phosphatases will be classified as to substrate specifity. Their regulation will be examined.